Over half a million people in the United States have died of AIDS since the beginning of the epidemic, and the number of people living with HIV infection is higher now than ever before. Currently, over 1 million adults and adolescents in the US are living with HIV. The majority of new HIV cases occur before age 25 and young Latinos are disproportionately affected. Compared to non-Latino white youths, Latino adolescents have 4 times the risk of HIV infection and, by young adulthood, more than 4 times the rate of AIDS diagnosis. Latinos are more likely to use substances in early adolescence and more likely to engage in unprotected sex than other ethnic groups, which increases their risk for HIV/AIDS. These disparities are persistent and represent a critical public health issue given the growing population of young Latinos in the US. Mexican Americans represent the largest subgroup of Latinos, yet longitudinal studies with Mexican American youth have been sparse due to a host of methodological barriers. The proposed longitudinal research resolves these issues to address important scientific gaps. By building on a rich, well-established, long-term cohort of Mexican American children and their parents, this project aims to understand whether and how adversity exposure in early life contributes to the emergence of substance use and HIV risk behaviors during adolescence. Towards this aim, we will gather detailed information on substance use and sexual risk-taking at ages 14y and 15.5y, when adolescents are sustaining the major social and biological transitions of the pubertal period. The strong study design builds on: (1) rich adversit data already collected during pregnancy and throughout childhood for this established cohort of Mexican American youth and their parents, combined with new equally rich data collection proposed in adolescence; (2) impressive participant retention to date in this hard-to-reach population; (3) ongoing assessing of puberty using leading-edge clinic-based methods obtained at multiple points in time; (4) the inclusion of new measures of stress responsively and pubertal hormones to better understand underlying bio physiological processes; and (5) the inclusion of key protective factors, including parental influences and cultural factors, that may buffer against risk for adolescent problem behaviors. Results from this project will yield important information about the emergence of substance use and sexual risk-taking within this highly vulnerable group. By focusing on potentially modifiable characteristics, this research has the potential to elucidate distinct areas to target for intervention to prevent risk-taking behaviors in adolescence and thereby reduce risk for HIV/AIDS and other STIs over the life course.